In order to appreciate the association between hypovitaminosis D and various adverse health outcomes, we require a thorough understanding of how common single nucleotide polymorphisms (SNPs) influence serum concentrations of 25-hydroxyvitamin D (25OHD). We undertook a systematic review of the literature in order to identify studies that examined 25OHD concentrations, and common SNPs. We found nine studies related to the vitamin D binding protein (group-specific component, GC), and five studies examining the vitamin D receptor (VDR). SNPs in a range of cytochrome P450 enzymes have also been examined in seven studies. Replicated findings have been found between 25OHD concentrations and (a) two SNPs in GC (rs4588, rs7041), (b) one SNP in VDR (rs10735810), and (c) one SNP in CYP27B1 (rs10877012). In light of these associations, it is feasible that optimal concentrations of 25OHD required to reduce disease outcomes may vary according to genotype. We speculate that recently identified U-shaped relationships between 25OHD concentrations and disease outcomes (i.e. increased risk at both high and low concentrations) may reflect a mixture of genotype-defined subgroups. Further research is required in order to clarify the genetic architecture underlying 25OHD serum concentrations, and to unravel the mechanisms of action responsible for these associations.